Project Summary A major goal of the DF/HCC GI SPORE is to identify and support projects that test clinically meaningful hypotheses and approaches aimed at reducing the incidence and mortality rates of GI cancers. To these ends, a flourishing Developmental Research Program (DRP) supports short-range studies to establish the results needed to facilitate well-validated, hypothesis-driven translational projects. The DRP's mission is to foster new endeavors in GI cancer research, enable promising new individual and collaborative efforts, promote novel technologies that enhance the community's research potential, and advance individual projects from pilot to sustainable status. An important aspect of this mission is to identify and stimulate interest in GI cancer research among established and junior investigators whose current focus may be different, but whose ideas, expertise, and preliminary data have the potential for fresh and significant impact on GI cancers. In addition to pilot funds and access to Core resources, projects and investigators benefit greatly from integration and collaboration with a thriving community of GI SPORE investigators. The DRP is led a highly qualified and invested committee that represents a full range of laboratory, clinical, and population sciences across the DF/HCC member institutions. This committee actively identifies the best talent, selects awardees through a fair and transparent process, and participates in ongoing review of pilot projects and programmatic goals. In the prior funding cycle, DRP support for 19 innovative, diverse, and specifically translational projects enabled novel discoveries, substantial contributions to the literature, and more than 20 federal and foundation grants to sustain and advance GI cancer research. The DRP incorporates the depth and flexibility necessary to maintain innovation in GI SPORE activities; notably, 3 of the 4 main projects in this renewal application grew from original DRP support. The DRP will continue to support novel research in GI cancer, with the following specific aims: 1) Solicit pilot projects in translational GI cancer research that demonstrate significant potential for reducing the prevalence, suffering, and death from the full spectrum of GI cancers; 2) Foster collaborative efforts among SPORE and other investigators to enable the development of innovative ideas and laboratory and treatment approaches; 3) Monitor the progress of developmental projects and provide investigators with critical, timely feedback; 4) Encourage and assist investigators with promising preliminary data arising from DRP support to compete for peer- reviewed extramural funding; and 5) When necessary and promising, promote the most meritorious DRP projects to full SPORE research projects.